| First Author | Chen L | Year | 2021 |
| Journal | Cell Death Differ | Volume | 28 |
| Issue | 6 | Pages | 1880-1899 |
| PubMed ID | 33462408 | Mgi Jnum | J:359870 |
| Mgi Id | MGI:6789968 | Doi | 10.1038/s41418-020-00714-7 |
| Citation | Chen L, et al. (2021) Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus. Cell Death Differ 28(6):1880-1899 |
| abstractText | Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2a(f/f), Kdm2a(-/-)) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a(-/-) increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a(-/-) mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a(-/-) macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a(-/-) mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance. |
